tbuckley/cabot-search huggingface dataset:
Leptomeningeal carcinomatosis and brain metastases in gastroesophageal carcinoma: A real-world analysis of outcomes, clinical and pathologic characteristics.
Authors: Thais Baccili Cury Megid, Zeynep Baskurt, Lucy Xiaolu Ma, Carly C. Barron, Marie-Philippe Saltiel, Abdul Rehman Farooq, Raymond Woo-Jun Jang, Eric Xueyu Chen, Rebecca KS Wong, Aruz Mesci, Hiroko Aoyama, Yvonne Bach, Xin Wang, Patrick Veit-Haibach, Ben X Wang, Sangeetha Kalimuthu, James Cotton, Elena Elimova
Journal: Journal of Clinical Oncology (2023)

2029 Background: Brain metastasis (BM) and Leptomeningeal Carcinomatosis (LC) are uncommon complications in gastroesophageal carcinoma (GEC) patients (pts). These patients have a poor prognosis and are challenging to study. We described the clinicopathologic features and outcomes in the largest real-world cohort of CNS metastasis in GEC pts. Methods: We conducted a single-center retrospective study of GEC pts treated at the Princess Margaret Cancer Centre from 2007 to 2021 who developed BM. Clinicopathologic characteristics and treatment modalities were reviewed. Survival was calculated from the date of BM or LC diagnosis until date of death/last follow-up using the Kaplan-Meier method. A multivariable Cox proportional hazards regression model was used to examine the association of baseline covariates and survival. Results: Of 3283 consecutive pts with GEC, 101 (3.08%) were diagnosed with BM and 20 with LC (0.61%). Most pts with BM were male (75.3%), non-Asian (93%), with a primary gastroesophageal junction tumor (47%) and adenocarcinoma histology (86%). Among pts with known HER2 status (N= 48), 60% were HER2 positive (defined as IHC 3+ or IHC 2+/FISH+). All patients with LC had adenocarcinoma histology; most were signet-ring subtype (85%), poorly differentiated (80%) histology and only 15% (2/13) were HER2 positive. Median survival was 0.8; 3.8; and 7.7 months (mo) in BM pts treated with palliative care only, radiation only and surgery followed by radiation, respectively (p&lt; 0.001). In LC, median survival was 0.7 mo in pts who had palliative care only (7/20) and 2.7 mo for those (13/20) who had whole brain radiation therapy (WBRT) (p .008). Multivariate analysis showed a higher probability of death in patients with number of BM ≥4 (p 0.02) and predicted superior survival in patients who received radiation and surgery followed by radiation (p 0.02). Conclusions: This is the most comprehensive summary of clinicopathologic characteristics and survival in patients with GEC and BM and LC disease to date. Biomarker analysis reveals an enriched frequency of HER2 expression in BM, while this is uncommon in pts with LC. BM pts who were treated with surgery followed by radiation had a significantly improved OS. WBRT benefited patients with LC over palliative care alone. These findings add to our understanding for the management of this understudied population with poor survival. [Table: see text]
Utilization and barriers to genomic profiling in breast cancer treatment among oncologists.
Authors: Taavy A. Miller, Cherrishe Brown-Bickerstaff, Madison Brown, Brooke Dulka, Yolaine Jeune-Smith, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2023)

e18882 Background: Genomic profiling (GP) may help identify novel, targeted breast cancer (BC) treatments. Increased utilization and technology of GP, including options such as next-generation sequencing (NGS) to identify mutations (e.g., PI3K, PTEN, and AKT) among patients with BC, has allowed for improved care and outcomes. Yet, there are limited standard guidelines for the application of GP, and little is known about current use and challenges in the United States (US). The objective of this study was to describe the utilization of and barriers to GP among US-based community oncologists. Methods: Three live meetings held between July and September 2022 convened oncologists to discuss trends in health care. Participants responded to survey questions online and onsite; not all participants answered every question. Results were aggregated and analyzed using descriptive statistics. Results: A total of 171 physicians participated (primary specialty: 56% hematology/oncology, 42% medical oncology, 2% other). The cohort is geographically diverse (Northeast 23%, Midwest 16%, South 43% and West 18%) and have a median of 18 years of experience. Most participants (92%) are using an NGS-based panel to test their patients with ER+ breast cancer for biomarkers (e.g., PI3K, AKT, and PTEN) and the most common panels utilized are indicated in the table. When treating BC, physicians indicated they most often order NGS-based tests prior to any treatment (33%) or prior to first-line treatment in the relapsed/metastatic setting (47%) (Table). Overall, the top two resources participants felt would increase their use of GP when treating patients with BC are: financial aid and reimbursement support (51%) and more clinical evidence on its utility for improving patient outcomes (48%) (Table). Education on the use of GP and decision support tools were also reported as resources that will increase utilization (34% each). Conclusions: Most oncologists are using GP when managing patients with BC, but the extent of utilization may be limited by barriers. Specifically, a lack of financial aid and/or reimbursement support and evidence on the utility to improve patient outcomes are reported as barriers. Despite high utilization of GP for patients with BC, there remains opportunity to increase uptake, such as more education and access to decision tools, which may increase the utilization and application in oncology settings. [Table: see text]
Impact of histology on the efficacy and safety of pembrolizumab (pembro) monotherapy for advanced urothelial carcinoma (UC) in the phase 3 KEYNOTE-045 and KEYNOTE-361 trials.
Authors: Patrizia Giannatempo, Jean-Pascal H. Machiels, Naoto Sassa, Jose Angel Arranz Arija, Yasuhisa Fujii, Wen-Pin Su, Bhumsuk Keam, Stephane Culine, Ying-Chun Shen, José Muñoz-Langa, David Leonid Sarid, Maureen J.B. Aarts, Fabio Calabro, Eli Rosenbaum, Olesya Goldman, Blanca Homet Moreno, Abhishek Amar Bavle, Jin Zhi Xu, Sun Young Rha
Journal: Journal of Clinical Oncology (2023)

4512 Background: For patients (pts) with advanced UC, pembro monotherapy has shown antitumor activity as first-line (1L) therapy in the phase 3 KEYNOTE-361 (NCT02853305) study of pembro ± platinum-based chemotherapy (chemo) vs platinum-based chemo and as second-line therapy in the phase 3 KEYNOTE-045 (NCT02256436) study of pembro vs investigator’s choice chemo. This exploratory analysis evaluated efficacy and safety of pembro monotherapy by UC histology in KEYNOTE-361 and KEYNOTE-045. Methods: KEYNOTE-361 enrolled pts with advanced UC and no prior systemic therapy; KEYNOTE-045 enrolled pts with advanced UC whose disease progressed or relapsed after 1L platinum-based chemo. Pure transitional cell (TC) and mixed predominant TC histology, as assessed by investigator, were allowed. Pembro monotherapy was given at a dose of 200 mg IV Q3W for up to 2 y or until disease progression, unacceptable toxicity, or withdrawal of consent in both studies. End points for this exploratory analysis were ORR, DOR, and PFS per RECIST v1.1 by central radiology assessment, and OS and safety in pts with pure TC or mixed predominant TC allocated to receive pembro monotherapy. Results: A total of 307 randomly assigned pts (280 [91.2%] pure TC histology; 27 [8.8%] mixed predominant TC histology) from KEYNOTE-361 and 268 pts (186 [69.4%] pure TC histology; 82 [30.6%] mixed predominant TC histology) from KEYNOTE-045 were included. Median follow-up for both studies was ≥32 mo. PFS, ORR, DOR, and OS for pembro were generally similar in pts with mixed predominant TC histology and pts with pure TC histology. In treated pts, grade 3-5 treatment-related AEs occurred at similar rates in KEYNOTE-361 (17.3% [48/277] pure TC; 18.5% [5/27] mixed predominant TC) and KEYNOTE-045 (16.9% [31/183] pure TC; 17.3% [14/81] mixed predominant TC). Conclusions: The observed clinical activity and safety profile of pembro monotherapy was generally consistent irrespective of histology in pts with UC in the KEYNOTE-361 and KEYNOTE-045 studies. Small sample size in some subgroups and limited data available to classify histology subgroups were limitations of this exploratory analysis. Clinical trial information: NCT02256436; NCT02853305 . [Table: see text]
Preoperative assessment in lung-limited metastatic patients with colorectal cancer: The Meta-Lung Score.
Authors: Pina Ziranu, Paolo Albino Ferrari, Francesco Guerrera, Pietro Bertoglio, Alessandro Tamburrini, Paraskevas Lyberis, Andrea Pretta, Giulia Grimaldi, Eleonora Lai, Massimiliano Santoru, Marco Dubois, Laura Riva, Fabio Bardanzellu, Aiman Alzetani, Luca Luzzi, Piergiorgio Solli, Piero Paladini, Enrico Ruffini, Roberto Cherchi, Mario Scartozzi
Journal: Journal of Clinical Oncology (2023)

3598 Background: Due to the inconsistent data on curative resection of isolated lung metastases (LM) from colorectal cancer (CRC) and the lack of specific recommendations, the therapeutic approaches for metastatic liver disease are mostly applied to LM treatment, despite differences in their biological behavior. Like Fong's criteria in CRC liver metastases, our study proposed a score associated with clinical outcomes in patients (pts) undergoing CRC lung metastasectomy, aiming to better pts' selection for surgery and the most appropriate therapeutic strategy. Methods: We retrospectively collected data from 260 pts (aged 18-85) who underwent CRC lung metastasectomy with curative intent from December 2002 to January 2022 at four Italian Centers: the Division of Thoracic Surgery at “A. Businco Cancer Center” in Cagliari, the Division of Thoracic Surgery at “Città della Salute e della Scienza” in Tourin, the Department of Thoracic Surgery at “IRCCS Azienda Ospedaliero-Universitaria” in Boulogne, and the Medical Oncology Unit of the University Hospital of Cagliari. Statistical analysis was performed with MedCalc (survival distribution: Kaplan-Meier; survival comparison: log-rank test; association between categorical variables: Fisher's exact test). Results: We analyzed the impact of different clinicopathological features on overall survival (OS). At the univariate analysis: higher baseline CEA levels (p = 0.0001), disease-free survival less than or equal to 12 months (m) (p = 0.0043), LM size larger than 2 cm (p = 0.0187), multiple resectable nodules (p = 0.0083), and positive nodal status of the primary tumor (p = 0.0011) were associated with poorer prognosis. In a Cox regression model, these five characteristics retained their independent role for OS (p &lt; 0.0001) and were chosen as criteria to be assigned one point each for clinical risk score. The 5-year survival rate in pts with 0 points was 88%, while no pts with a 5-points score survived at 2 years. Based on the 0-2 versus 3-5 score range, we obtained a significant difference in median OS: 101.7 m (95%CI 64.6 - 101.7) vs. 39.5 m (95%CI 27.3 - 87.5) respectively (p &lt; 0.0001) stratifying pts into good and poor prognosis. Conclusions: The Meta-Lung Score appeared to be an exciting prognostic tool in selecting CRC pts’ candidates for radical surgical treatment when LM were diagnosed. Whether early surgery should be considered in pts with a score 0-2, the same choice should be taken with caution in pts with a score 3-5, for whom early chemotherapy would allow better assessment of tumor biology and appropriate selection for surgery.[Table: see text]
Liver directed therapies in primary and metastatic liver cancer: A rural academic institution experience.
Authors: Zabila Saeed, Aidan Michael Burke, David Meyer, Mahvish Muzaffar
Journal: Journal of Clinical Oncology (2023)

e16188 Background: Liver-directed therapies (LDT) are well established in the treatment of primary and secondary hepatic malignancies and are developed for potentially curative intent, bridging for definitive therapy or palliation. They are used either in isolation usually for hepatocellular carcinoma (HCC) or in combination with systemic chemotherapy and/or surgery. We conducted a retrospective study at our academic institution that serves ethnic minorities and patients with high BMI and multiple major co-morbidities. Methods: All patients who underwent liver-directed therapy at ECU Health Medical Center from the year 2010 to 2020 were included in this study. Total of 196 patients were identified of which 96 met the eligibility criteria. That criteria included all patients who have undergone any type of liver directed therapy in primary and mainly metastatic gastrointestinal liver cancer. We conducted descriptive univariate analysis, cox regression and Kaplan-Meier survival analysis. Results: The study cohort had 63% (n=60) with primary HCC and 38% (n=36) with metastatic liver cancer predominantly colorectal cancer. Median age at diagnosis was 68 yrs. (65.3-69.5), 58% were Caucasian, 38% were black and 2% were other ethnic groups. 68% of the patient were male and 31% were female. ECOG performance status of 1 in 60% of the cohort. 50% of the cohort had 3 major comorbidities other than cirrhosis and hepatitis. Mean body mass index (BMI) was &gt;25 kg/m2. 43% of the patient (n=41) had multiple barriers to care. Patients with primary HCC, 45% had hepatitis C and 48 % had non-viral causes in 60 patients. Child- Pugh A in 67% (n=40), B in 30% (18) and C in 3% (n=3). 70% of non-HCC cohort has colorectal and cholangiocarcinoma. All patient in non-HCC group received chemotherapy and 52% of HCC cohort received systemic therapy. 55% (n= 43) of the patients underwent Y-90 and 55% (n= 53) underwent other types of liver directed therapies, most common being TACE. 62% of the patient underwent 1 treatment and 38% had &gt;2 LDT. Multivariate analysis showed that age (p-value, 0.0229) and type of liver directed therapy ( p-value, 0.0212) are statistically significant in the HCC cohort. In the non-HCC cohort, patients with high BMI (P-value=0.0050) had poor outcome and was statistically significant. Conclusions: Liver directed therapy is a reasonable option for patients with HCC and non-HCC metastatic disease. According to our study, it improves median survival in non-HCC patients. It includes rural population with high BMI, major comorbidities and multiple barriers to care. In this study, 38% of patients were African Americans who are usually underrepresented in majority of studies. Limitations of the study include retrospective nature of the analysis and heterogenous group. In future clinical trials, ethnic minorities should be equally represented to advance health equity and to apply real word data to the populations we serve.
A novel platform to enrich for tumor-specific T cells in non–small-cell lung cancer.
Authors: Stephanie J Hachey, Alexander G Forsythe, Ali Mahtabifard, Hari B. Keshava, Christopher C.W. Hughes
Journal: Journal of Clinical Oncology (2023)

2556 Background: To induce robust cellular immunity against non-small cell lung cancer (NSCLC), the leading cause of cancer-related death in the US, we have developed an innovative cell-based therapeutic platform technology to generate polyclonal, neoantigen-reactive T cells in vitro. Methods: Surgically resected NSCLC tissue and peripheral matched blood were collected from 17 patients under an IRB-approved protocol. From 3 of the patient-derived NSCLC specimens, methods were tested to enhance immunogenicity and stimulate neoantigen-specific immune responses. We then use a novel, human vascularized microtumor (VMT) platform to assess the sensitivity of tumor cells to T-cell mediated attack at the individual patient level. Results: The therapeutic platform induced a significant increase in T cell proliferation, interferon-gamma secretion, and blast phenotype of lymphocyte populations compared to T cells primed by standard methods. Interestingly, for one patient, immunosuppression of the T cell response with concomitant increase in CD96, an immune checkpoint receptor implicated in lung cancer progression, was observed in the tumor. Importantly, using sequencing data from one patient, an analytical and machine learning pipeline detected putative neoantigens using our therapeutic platform technology and not with standard methods. Conclusions: The therapeutic platform can be used to directly generate cell-based immunotherapies and to facilitate neoantigen discovery and development of targeted cancer immunotherapies. Our goal is to advance novel approaches to effectively mobilize anti-tumor immunity and overcome treatment resistance in NSCLC.
Retrospective analysis of the multikinase inhibitor (MKI) pazopanib in differentiated thyroid carcinoma (DTC) in the beyond-first-line setting.
Authors: Jyothik Varun Inampudi, Himil Mahadevia, Alexandra Stone, Alana Toby, Hiren Koshiya, Jaydeepbhai Patel, Vivek Pandav, Shenduo Li, Sarika Rao, Ana-Maria Chindris, Rami Manochakian, Yanyan Lou, Yujie Zhao
Journal: Journal of Clinical Oncology (2023)

e18097 Background: Sorafenib and lenvatinib are FDA-approved MKIs for locally recurrent or metastatic, progressive, DTC refractory to radioactive iodine treatment. Cabozantinib showed a survival benefit in radioiodine-refractory DTC previously treated with sorafenib and/or lenvatinib and was granted FDA approval. Our study aims to investigate the benefit of other MKIs in DTC beyond the first-line setting. Methods: DTC patients (pts) treated with multiple lines of MKIs from August 2018 to July 2022 at Mayo Clinic across all sites were identified. Electronic medical records were reviewed. 6-month, 12-month, and 18-month progression-free survival (PFS) were calculated for all lines of therapy using RECIST 1.1 criteria. Results: Among the 9 pts identified, 4 were male. The median age was 65 years (43-75). Most pts (60%) had papillary thyroid cancer. All pts received lenvatinib as first line treatment. The 6, 12 and 18-month PFS were 89%, 89%, and 55% respectively. 6 pts discontinued lenvatinib due to progression of disease (PD). 3 pts discontinued it due to adverse effects (AEs), which included hemoptysis (1 pt), severe rash (1 pt) and multiple psychiatric manifestations (1 pt). 8 pts received pazopanib, and 1 patient received cabozantinib with ipilimumab (1 dose) and nivolumab (6 months - discontinued due to myocarditis) as second-line therapy. Among them, 1 patient received pembrolizumab plus everolimus for 2 months before receiving pazopanib. The 6, 12 and 18-month PFS were 55%, 22%, and 11% respectively. All pts ceased treatment due to eventual PD, and there were no toxicity-related discontinuations. 5 pts subsequently received third-line MKIs, including cabozantinib (3 pts), pazopanib (1 pt), and lenvatinib (1 pt). The pt who received lenvatinib had discontinued it as first line therapy due to toxicity. The 2 pts treated with third-line cabozantinib and the pt rechallenged with lenvatinib showed no PD at 12-months and no toxicity related discontinuation. Conclusions: Pazopanib was associated with durable PFS and good tolerability when offered after PD or intolerance on lenvatinib in this retrospective analysis, warranting a randomized prospective study. [Table: see text]
A propensity score–matched analysis to evaluate the benefit of adjuvant therapy on disease progression of esophageal squamous cell carcinoma after R0 esophagectomy.
Authors: Yuqin Cao, Qingqing Hu, Yajie Zhang, Chengqiang Li, Yuan Zhou, Yongjing Zhang, Hong Qiu, Hecheng Li
Journal: Journal of Clinical Oncology (2023)

e16071 Background: The impact of adjuvant therapy (AT) on patients’ disease progression with esophageal squamous cell carcinoma (ESCC) after R0 resection remains controversial in clinical practice. The study aims to evaluate the benefits of AT on recurrence or death through propensity score (PS) matched analyses. Methods: A cohort of patients who have undergone R0 esophagectomy without neoadjuvant therapy for ESCC was identified at the tertiary hospital in China between 2013 and 2020. Patients’ demographic, clinical, surgical, pathological and follow-up data were retrieved from a prospectively maintained database. PS for each patient was calculated by the generalized linear regression model including all potential confounders (age, sex, body mass index, smoking history, alcohol consumption, Eastern Cooperative Oncology Group performance score, baseline comorbidities, hospitalization days, tumor location, size, pathological stage T, N and differentiation grade). PS was stratified into four groups (PS &lt; 0.20, 0.20≤PS &lt; 0.30, 0.30≤PS &lt; 0.40, and PS≥0.40) based on distributions. Patients with and without AT were matched by the nearest neighbor PS with caliper 0.05 to evaluate rates of recurrence-free survival (RFS) for overall patients and patients across four PS groups. RFS was defined as the time from date of curative surgery to the time of recurrence or death. Results: In total, 523 patients were identified and 162 (30.9%) of those patients received AT. A total of 312 (60.0%) patients experienced recurrence or death with a median follow-up of 4.15 years (interquartile range: 2.92-4.73 years). Patients with younger ages, shorter hospitalization, larger tumor size, advanced pathological T and N stages, poorly differentiated tumors were more likely to receive AT (all p &lt; 0.05). The mean PS was 0.39 (standard deviation [SD] 0.16) for AT group and 0.27 (SD 0.15) for non-AT group. A total of 274 patients (137 AT and 137 non-AT) were matched. Before matching, AT group tended to have a worse RFS compared with non-AT group (median RFS: 1.84 years vs 2.67 years, p = 0.06). However, after PS matching, AT group showed a significantly better RFS compared with non-AT group (median RFS: 2.41 vs. 1.89 years, p = 0.02). In the subgroup analyses, the benefits of AT were mostly consistent with the whole group, except for patients with PS &lt; 0.20 where AT tended to have worse RFS. Moreover, for PS≥0.40 subgroup, a significantly better RFS was observed in AT group compared with non-AT group (median RFS: 3.52 vs. 1.53 years, p &lt; 0.01). Conclusions: Adjuvant therapy had a benefit on delaying disease progression for Chinese patients with ESCC after R0 esophagectomy, especially for patients with a higher PS score.